Search Results (98)

The aim of this study was to examine associations involving serum proprotein convertase subtilisin/kexin type 9 (PCSK9) in metabolic disturbances observed in women with polycystic ovary syndrome (PCOS), with particular emphasis on the potential impact of tobacco smoke exposure. The study included 88 women: 60 with PCOS (23 smokers and 37 non-smokers) and 28 without PCOS. Selected biochemical and molecular biomarkers related to lipid metabolism, oxidative stress, and inflammation were assessed. No significant differences in PCSK9 levels were observed among non-smoking women with PCOS, smoking women with PCOS, and non-smoking women without PCOS. However, in women with PCOS, excess body weight and insulin resistance were associated with increased PCSK9 concentrations. Significant correlations between PCSK9, lipid profile parameters, and the Castelli and triglycerides-glucose indices suggest a potential role of PCSK9 as a biomarker of dyslipidemia and cardiometabolic risk. Elevated PCSK9 levels may contribute not only to increased low-density lipoprotein cholesterol but also to enhanced formation of oxidized low-density lipoprotein, which is particularly detrimental to cardiovascular and metabolic health. Vitamin D levels were more strongly associated with smoking status and insulin resistance than with excess body weight. Overall, these findings indicate that PCSK9 regulation in PCOS may be driven predominantly by metabolic factors rather than PCOS status or smoking per se, and that metabolic status and vitamin D deficiency should be considered when assessing cardiometabolic risk in this population. Full article

Background: Vitamin D (VD) plays a central role in calcium homeostasis during pregnancy and has been implicated in redox-related biological processes. While VD deficiency (VDD) has been consistently associated with adverse pregnancy outcomes, the relationships between VD insufficiency (VDI), maternal antioxidant-related biomarkers, and neonatal outcomes remain incompletely characterized, particularly during the third trimester. Objective: To determines the prevalence of VDI in third-trimester pregnant women and to examine its associations with antioxidant-related markers and selected neonatal outcomes. Methods: A cross-sectional study was conducted among pregnant women in the third trimester attending a tertiary referral hospital in Mexico City. Maternal serum 25-hydroxyvitamin D (25-OHD) concentrations were measured, along with a panel of redox-related markers, including 2,2-diphenyl-2-2picrylhydrazyl (DPPH) radical scavenging activity, reduced glutathione (GSH), glutathione S-transferase (GST), glutathione peroxidase (GPx), and oxygen radical absorbance capacity (ORAC). Neonatal anthropometric parameters were recorded at birth. Associations between maternal VD status, redox-related markers, environmental factors, and neonatal outcomes were evaluated using appropriate statistical analyses. Results: A high prevalence of VDI was observed in the study population. Maternal VDI was associated with lower activities of GSH, GST, and GPx. Passive exposure to tobacco smoke and season of sampling were also associated with lower VD concentrations. Neonates born to women with VDI had higher birth weight compared with those born to women with sufficient VD concentrations. Maternal serum 25-OHD concentrations correlated positively with selected antioxidant enzyme activities. Conclusions: In this cohort of third-trimester pregnant women, VDI co-occurred with environmental factors, differences in maternal redox-related markers, and selected neonatal outcomes. These findings support an associative framework in which suboptimal VD status during the third trimester is accompanied by variations in redox-related markers. Longitudinal and mechanistic studies are needed to clarify the temporal sequence and biological relevance of these associations. Full article

Head and neck cancer represents a heterogeneous group of malignancies. Oral squamous cell carcinoma (OSCC) is the most prevalent form of head and neck cancer, with a rising incidence in recent years. Risk factors for developing OSCC include exposure to carcinogens, such as alcohol and tobacco products, that can lead to molecular alterations in the oral mucosa and progression from premalignant lesions to invasive phenotypes. Despite the relative curative potential of localized OSCC, the overall prognosis of OSCC has not significantly improved for decades due to a frequently delayed diagnosis and limited targeted treatment options. There remains a need to better characterize the molecular biomarkers of OSCC progression, especially in dysplastic mucosal lesions, before their malignant transformation. In this review, we discuss several molecular biomarkers highly implicated in OSCC tumorigenesis that have demonstrated correlation with clinicopathological parameters and clinical outcomes. These biomarkers are typically involved in vital pathways of carcinogenesis, including cell cycle control, growth factor signaling, and stress responses. They include ubiquitous cancer biomarkers such as p53 and PTEN, as well as those more specific to OSCC, such as DJ-1 and Cornulin. Collectively, we envision that a diverse panel of these biomarkers can provide the greatest clinical benefit in enhancing early detection and prognostic accuracy, while some individual biomarkers may also serve as therapeutic targets for personalized approaches to head and neck cancers. Full article

Cadmium (Cd) is a persistent toxic metal that bioaccumulates in human tissues and may disrupt redox and endocrine pathways, yet the metabolic mechanisms linking Cd exposure to both endothelial and prostate dysfunctions remain insufficiently defined. This study investigated whether chronic occupational Cd exposure alters methylated arginine metabolism and prostate-specific antigen (PSA) levels, indicating a shared toxicometabolic axis. A total of 150 male workers were enrolled, including 75 metallurgical employees with documented Cd exposure and 75 matched controls. All participants were non-smokers, eliminating confounding from tobacco-related oxidative or endocrine effects. Urinary Cd concentrations were quantified using Inductively Coupled Plasma–Mass Spectrometry (ICP–MS), and serum asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), L-arginine, citrulline, and PSA were measured by Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) and electrochemiluminescence. The use of Inductively Coupled Plasma–Mass Spectrometry for cadmium quantification and LC-MS/MS for methylated arginine profiling provided high analytical specificity and sensitivity, strengthening the validity of biomarker measurements. Correlation and multivariable analyses adjusted for age and body mass index. Cd-exposed workers demonstrated significantly elevated urinary Cd, PSA, ADMA, and SDMA levels, alongside reduced arginine/ADMA ratios, consistent with impaired nitric oxide bioavailability. Urinary Cd strongly correlated with PSA and ADMA levels. These findings indicate that Cd may disrupt the nitric oxide pathway and elevates PSA, supporting a mechanistic link between vascular and prostate stress. Combined ADMA, SDMA, and PSA profiling may serve as an early biomarker panel for Cd-related metabolic injury in occupational settings. Full article

Developmental programming, shaped by environmental and lifestyle stressors during prenatal life, is increasingly recognized as a major contributor to non-communicable diseases (NCDs) later in life. Oxidative stress, one of key mechanisms linking these stressors to fetal metabolomic reprogramming and disease pathogenesis, leaves measurable metabolomic signatures that reflect disrupted redox balance. Alterations in glucose, lipid, and amino acid metabolism and antioxidant response could reveal the main pathways driving NCD development. This review summarizes epidemiological studies that have investigated biochemical responses of the prenatal exposure to metals, air pollution, and tobacco smoke and e-cigarette vapor in maternal–placental–fetal compartments using a metabolomic approach. Summarized studies indicate that maternal exposure to metals primarily disrupts amino acid pathways related to one-carbon metabolism, glutathione synthesis, and oxidative stress defense, while air pollution, particularly fine particulate matter, mainly affects lipid oxidation, fatty acid β-oxidation, and amino acid and carbohydrate metabolism. Tobacco smoke and e-cigarette vapor induce widespread disturbances involving reduced citric acid cycle intermediates, altered acylcarnitines and phospholipids, and impaired antioxidant capacity, collectively promoting oxidative damage and inflammatory signaling. The identification of these metabolome alterations might contribute to a deeper understanding of the toxicity and biological impact of environmental stressors on offspring health. These results may eventually lead to the identification of early biomarkers and to the development of therapeutic strategies aimed at reducing NCD risk. Full article

Background/Objectives: Lead, a toxic heavy metal, is widely recognized as a hazardous environmental contaminant capable of disrupting physiological homeostasis by altering stress response mechanisms and impairing pulmonary function. A comparable detrimental factor is tobacco smoking, which represents one of the most prevalent addictions worldwide. The presented study aimed to evaluate the combined impact of cigarette smoking and occupational lead exposure on selected oxidative stress biomarkers and pulmonary function parameters. Methods: 453 male employees working in a zinc smelter were recruited for participation in the study. Participants were subsequently divided into two groups: current smokers (n = 209) and former smokers (n = 244). Each group was then further subdivided according to blood lead concentration into subgroups with high (>35 μg/dL) and low (<35 μg/dL) lead levels. Venous blood samples were collected for biochemical analysis of oxidative stress parameters, including total oxidant status (TOS), malondialdehyde (MDA), protein thiol content (PSH), total antioxidant capacity (TAC), and the oxidative stress index (OSI). In addition, spirometric evaluation was conducted. Results: Former smokers demonstrated significantly more favorable oxidative stress profiles and superior spirometric outcomes compared with current smokers. No statistically significant associations were observed between lead exposure levels and either biochemical or spirometric parameters. Conclusions: Cigarette smoking appears to exert a stronger adverse influence on oxidative balance and pulmonary function than occupational lead exposure. Full article

Background: Chronic Obstructive Pulmonary Disease (COPD) remains a leading cause of morbidity and mortality worldwide, particularly in low- and middle-income countries (LMICs), where both tobacco and biomass smoke exposure are major risk factors. While spirometry is the diagnostic gold standard, reliable non-invasive biomarkers are needed for early detection and disease monitoring. The soluble receptor for advanced glycation end-products (sRAGE), a circulating decoy receptor with anti-inflammatory activity, has shown potential in this context. Methods: In this prospective, exposure-stratified, cross-sectional study, 150 adults were enrolled into four groups of 25 each—tobacco-smoke COPD, male tobacco-exposed controls, biomass-smoke COPD, and female biomass-exposed controls—along with 50 healthy controls (25 males, 25 females). Participants underwent clinical evaluation, spirometry, and serum sRAGE quantification (ELISA). Systemic inflammation was assessed using neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Correlation and receiver operating characteristic (ROC) analyses determined diagnostic performance. Results: Serum sRAGE levels were significantly lower in tobacco-induced (545 ng/mL) and biomass-induced COPD (540 ng/mL) versus controls (1207–1462 ng/mL; p < 0.001). sRAGE correlated positively with FEV₁, FVC, and FEV₁/FVC (r = 0.54–0.75, p < 0.001), and negatively with CAT, mMRC, and SGRQ-C. ROC analysis showed excellent discrimination (AUC = 0.990; 94% sensitivity; 96% specificity at 946 ng/mL cutoff). Conclusions: Serum sRAGE is a robust, non-invasive biomarker for COPD diagnosis and severity assessment across exposure phenotypes. Its integration into clinical practice may enhance early detection and risk stratification, particularly in LMICs. Full article

This study aimed to examine the associations between distinct tobacco smoke exposure (TSE) biomarkers and healthcare utilization patterns in U.S. children ages 3–11 years with and without current asthma. Secondary data from the 2013–2016 National Health and Nutrition Examination Survey were analyzed (N = 2838). TSE biomarkers included serum cotinine, urinary total nicotine equivalents (TNE2), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), the NNAL/TNE2 ratio, and the N-acetyl-S-(2-cyanoethyl)-L-cysteine (2CyEMA)/TNE2 ratio. We conducted Poisson regression analyses to examine the associations between each biomarker and healthcare visits and hospitalizations within the past 12 months, adjusting for sociodemographic and home TSE covariates. Children without asthma who had higher urinary TNE2 levels (adjusted incidence rate ratio [aIRR] = 1.03, 95% confidence interval [CI] = 1.02–1.04) and children with asthma who had higher urinary 2CyEMA/TNE2 ratio levels (aIRR = 1.05, 95%CI = 1.03–1.07) were at an increased risk of having more healthcare visits. Children without asthma who had higher serum cotinine (aIRR = 1.21, 95%CI = 1.07–1.37) and higher 2CyEMA/TNE2 ratio levels (aIRR = 1.25, 95%CI = 1.14–1.37) were at an increased risk of hospitalizations. Children with asthma who had higher NNAL/TNE2 ratio levels (aIRR = 1.52, 95%CI = 1.11–2.09) were at increased risk of hospitalizations. It is important to consider comprehensive biomarkers of TSE in children, such as TNE, tobacco-specific nitrosamines, and volatile organic compounds, along with healthcare utilization patterns. Child TSE reduction policies are urgently needed. Full article

Cardiovascular diseases (CVDs) are increasingly being defined not only in terms of metabolic or purely vascular disorders, but also as complex immunometabolic disorders. One of the most groundbreaking discoveries in recent years is the role of neutrophil extracellular networks (NETs/NENs) as a key link between chronic vascular wall inflammation and thrombotic processes. In this article, we present a synthetic overview of the latest data on the biology of NETs/NENs and their impact on the development of atherosclerosis, endothelial dysfunction, and the mechanisms of immunothrombosis. We highlight how these structures contribute to the weakening of atherosclerotic plaque stability, impaired endothelial barrier integrity, platelet activation, and the initiation of the coagulation cascade. We also discuss the modulating role of classic risk factors such as hypertension, dyslipidemia, and exposure to tobacco smoke, which may increase the formation or hinder the elimination of NETs/NENs. We also focus on the practical application of this knowledge: we present biomarkers associated with the presence of NETs/NENs (cfDNA, MPO–DNA complexes, CitH3, NE), which may be useful in diagnostics and risk stratification, and we discuss innovative therapeutic strategies. In addition to classic methods for indirectly inhibiting NET/NEN formation (antiplatelet, anti-inflammatory, and immunometabolic agents), we present experimental approaches aimed at their neutralization and removal (e.g., DNase I, elastase, and myeloperoxidase inhibitors). We pay particular attention to the context of cardiac and cardiac surgical procedures (Percutaneous Coronary Intervention-PCI, coronary artery bypass grafting-CABG), where rapid NET/NEN bursts can increase the risk of acute thrombotic complications. The overall evidence indicates that NETs/NENs represent an innovative and promising research and therapeutic target, allowing us to view cardiovascular diseases in a new light—as a dynamic interaction of inflammatory, atherosclerotic, and thrombotic processes. This opens up new possibilities in diagnostics, combination treatment and personalisation of therapy, although further research and standardization of detection methods remain necessary. Full article

Background: Since the emergence of e-cigarettes on the market in the early 2000s, the prevalence of e-cigarette use has increased globally. The health risks of using e-cigarettes have been increasingly revealed; however, the health effects on non-users exposed to e-cigarettes are less known. Methods: A systematic review was conducted of peer-reviewed articles from 2004 to October 2024 from PubMed and Embase. We focused on the studies that described health outcome measures among non-smokers/vapers exposed to secondhand e-cigarettes. We excluded animal studies and those that did not include human participants. We also omitted studies with financial conflicts of interest with the tobacco industry. Results: Of the 8635 studies we found in our search, 16 were included in the final review. Study designs included in our review included a case study, a cohort, eight experimental, four cross-sectional studies, and two observational studies. Health outcome measures were self-reported health symptoms and biomarkers. Ten out of fourteen studies examined respiratory health risks, six described immunological effects, two examined cardiovascular risks, and one explored mental health effects. Self-reported health symptoms such as bronchitis, shortness of breath, asthma, throat irritations, ear infections, and mental health disorders were observed among secondhand e-cigarette exposures when compared with controls. Biomarker measures varied among studies, except for cotinine concentrations of non-smokers/vapers exposed to secondhand e-cigarettes, which were likely to be higher than non-exposed. However, all studies encountered potential limitations. Conclusions: Our review found that secondhand e-cigarette exposure is not harmless and may have negative health consequences. However, higher-quality prospective studies remain essential to examine long-term secondhand exposure. Full article

Substance use during pregnancy is an increasingly important yet under-recognized threat to maternal and child health. This narrative review synthesizes the current evidence available on the epidemiology, pathophysiology, clinical management, and policy landscape of prenatal exposure to alcohol, tobacco, opioids, benzodiazepines, cocaine, cannabis, methamphetamines, and other synthetic drugs. All major psychoactive substances readily cross the placenta and can remain detectable in breast milk, leading to a shared cascade of obstetric complications (hypertensive disorders, placental abruption, pre-term labor), fetal consequences (growth restriction, structural malformations), and neonatal morbidities such as neonatal abstinence syndrome and sudden infant death. Mechanistically, trans-placental diffusion, oxidative stress, inflammatory signaling, and placental vascular dysfunction converge to disrupt critical neuro- and cardiovascular developmental windows. Early identification hinges on the combined use of validated screening questionnaires (4 P’s Plus, CRAFFT, T-ACE, AUDIT-C, TWEAK) and matrix-specific biomarkers (PEth, EtG, FAEE, CDT), while effective treatment requires integrated obstetric, addiction, and mental health services. Medication for opioid use disorders, particularly buprenorphine, alone or with naloxone, confers superior neonatal outcomes compared to methadone and underscores the value of harm-reducing non-punitive care models. Public-health strategies, such as Mexico’s “first 1 000 days” framework, wrap-around clinics, and home-visiting programs, demonstrate the potential of multisectoral interventions, but are hampered by structural inequities and punitive legislation that deter care-seeking. Research gaps persist in polysubstance exposure, culturally tailored therapies, and long-term neurodevelopmental trajectories. Multigenerational, omics-enabled cohorts, and digital longitudinal-care platforms represent promising avenues for closing these gaps and informing truly preventive perinatal health policies. Full article

This review aims to provide a comprehensive overview of how oxidative stress drives inflammation, structural remodeling, and clinical expression of childhood asthma, while critically appraising emerging redox-sensitive biomarkers and antioxidant-focused preventive and therapeutic strategies. Oxidative stress arises when reactive oxygen species (ROS) and reactive nitrogen species (RNS) outpace airway defenses. This surplus provokes airway inflammation: ROS/RNS activate nuclear factor kappa-B (NF-κB) and activator protein-1 (AP-1), recruit eosinophils and neutrophils, and amplify type-2 cytokines. Normally, an antioxidant network—glutathione (GSH), enzymes such as catalase (CAT) and superoxide dismutase (SOD), and nuclear factor erythroid 2-related factor 2 (Nrf2)—maintains redox balance. Prenatal and early exposure to fine particulate matter <2.5 micrometers (µm) (PM_2.5), aeroallergens, and tobacco smoke, together with polymorphisms in glutathione S-transferase P1 (GSTP1) and CAT, overwhelm these defenses, driving epithelial damage, airway remodeling, and corticosteroid resistance—the core of childhood asthma pathogenesis. Clinically, biomarkers such as exhaled 8-isoprostane, hydrogen peroxide (H₂O₂), and fractional exhaled nitric oxide (FeNO) surge during exacerbations and predict relapses. Therapeutic avenues include Mediterranean-style diet, regular aerobic exercise, pharmacological Nrf2 activators, GSH precursors, and mitochondria-targeted antioxidants; early trials report improved lung function and fewer attacks. Ongoing translational research remains imperative to substantiate these approaches and to enable the personalization of therapy through individual redox status and genetic susceptibility, ultimately transforming the care and prognosis of pediatric asthma. Full article

Background: Occupational bronchopulmonary diseases (OBPDs)—including pneumoconiosis, silicosis, and occupational COPD—remain a pressing public health issue, especially in regions with intensive mining, metallurgy, and construction industries. Caused by chronic inhalation of fibrogenic dusts, these conditions are often diagnosed at late stages, resulting in irreversible lung damage and diminished work capacity. Methods: A scoping review was performed using the Arksey and O’Malley framework, with methodological refinements from the Joanna Briggs Institute. Following PRISMA-ScR guidelines, we searched PubMed, Scopus, and gray literature for publications from 2014 to 2024. After screening 1761 records and full-text review, nine studies were included in the final synthesis, comprising two systematic reviews, two narrative literature reviews, and five observational studies. Results: Key risk factors identified included prolonged exposure to silica and coal dust, tobacco use, and genetic susceptibility. Diagnostic delays were attributed to the underuse of high-resolution CT and exhaled nitric oxide analysis. Several studies highlighted the diagnostic value of oxidative stress and inflammatory markers (e.g., IL-6, TNF-α). Nutritional rehabilitation and polyphenol-enriched herbal therapies were associated with improved respiratory function and quality of life. However, these strategies remain underutilized, particularly in low-resource settings. Conclusions: A coordinated, biomarker-driven approach integrating early diagnosis, dust exposure control, and tailored rehabilitation is urgently needed. Multidisciplinary models may reduce the clinical and socioeconomic burden of OBPDs. Full article

Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infections (ALRIs) in young children, especially bronchiolitis, with significant global health and economic impact. Increasing evidence links early-life RSV infection to long-term respiratory complications, notably recurrent wheezing and asthma. This narrative review examines these associations, emphasizing predictive factors and emerging biomarkers for risk stratification. Early RSV infection can trigger persistent airway inflammation and immune dysregulation, increasing the likelihood of chronic respiratory outcomes. Risk factors include severity of the initial infection, age at exposure, genetic susceptibility, prematurity, air pollution, and tobacco smoke. Biomarkers such as cytokines and chemokines are showing promise in identifying children at higher risk, potentially guiding early interventions. RSV-related bronchiolitis may also induce airway remodeling and promote Th2/Th17-skewed immune responses, mechanisms closely linked to asthma development. Advances in molecular profiling are shedding light on these pathways, suggesting novel targets for early therapeutic strategies. Furthermore, passive immunization and maternal vaccination offer promising approaches to reducing both acute and long-term RSV-related morbidity. A deeper understanding of RSV’s prolonged impact is essential to develop targeted prevention, enhance risk prediction, and improve long-term respiratory health in children. Future studies should aim to validate biomarkers and refine immunoprophylactic strategies. Full article

Introduction: This study aimed to analyze exhaled breath condensate (EBC) for 8-oxoguanine (8-oxoGua), an oxidative stress biomarker among waterpipe (WP) smokers. Methods: In a within-subject pre-post exposure design, thirty waterpipe smokers completed two 45 min laboratory sessions. EBC was analyzed for 8-oxoGua before and after WP smoking. Median differences between time points (pre vs. post) were assessed using the Wilcoxon sign rank test, with significance defined as p < 0.05. Results: The analysis included 59 WP smoking sessions. Participants had a median age of 24 years (IQR: 21–25), with 62.1% being female. Most had a bachelor’s degree or less (62.1%), and over half were students (55.2%), while 34.5% were employed. The average age for first WP use was 18.6 years, with participants reporting a median of three WP smoking sessions per month. Results indicate a median increase in 8-oxoGua among participants from 5.4 ng/mL (IQR: 8.8) before the smoking session to 7.6 ng/mL after (IQR: 15.7; p < 0.001). Conclusions: This study is the first to examine 8-oxoGua in EBC. Findings provide strong evidence of WP smoking’s contribution to oxidative stress in the airways. It justifies the use of EBC to study the exposure to markers of oxidative stress with emerging tobacco use methods such as the waterpipe. Full article